The research proposed in this competing renewal application for an ADAMHA Research Scientist Award is based upon grants currently funded by NIDA and NIAAA which focus upon studies of polydrug abuse in women and female rhesus monkey. The experimental analysis of polydrug use patterns of marihuana, alcohol and tobacco will be carried out under controlled research ward conditions with operant behavioral procedures. The consequences of chronic cocaine abuse will be examined in patients and in a primate model of drug abuse where polydrug abuse cannot influence data obtained. The NIDA Clinical Research Center studies will also evaluate drug interactions and the role of premenstrual dysphoria on drug self-administration by women. Assessments of the efficacy and safety for adjunctive pharmacotherapies for cocaine, opiate and polydrug abuse will be evaluated in both patients and in female rhesus monkey. The NIAAA supported research grant program will examine alcohol effects on reproductive hormones in women as well as ethanol-induced alterations in neuroendocrine function which may modulate the reinforcing properties of alcohol. Effects of acute alcohol intoxication on pituitary, adrenal and gonadal hormones will be examined utilizing provocative tests of hypothalamic, pituitary, ovarian and adrenal function. Provocative tests will also be employed to determine mechanisms of alcohol-induced disruption of normal menstrual function in women of childbearing age and alcohol- induced alterations in endocrine function in post-menopausal women. Multidisciplinary approaches will be utilized in both the NIDA and NIAAA supported research Scientists from a variety of disciplines, including psychiatry, psychology, internal medicine, endocrinology, neurology, pharmacology, nursing and the social sciences, will participate in these investigations. The overall objectives of the proposed research are to clarify the behavioral and biologic determinants and consequences of substances abuse and to improve our understanding of the way in which drugs act as reinforcers leading to their self-administration. Plans for professional growth include advanced study in the fields of neuroendocrinology, magnetic resonance imaging and magnetic resonance spectroscopy.